Obesity and tobacco smoking represent two of the most substantial causes of morbidity and mortality in the United States. Stress and diminished self-control are two important factors associated with obesity, tobacco smoking, and other behaviors with addictive potential. However, no studies have systematically examined the neural correlates of self-control, stress, food-related, and smoking-related responses in obese and tobacco smoking subjects. Here we propose examining obese smokers, obese non-smokers, normal weight smokers, and normal weight non-smokers in a guided imagery paradigm that we have adapted for functional magnetic resonance imaging (fMRI) in conjunction with behavioral measures of self-control and related constructs (e.g., impulsivity and decision-making). Our prior fMRI work using the guided imagery paradigm has examined how brain activation patterns to stress, drug cue, or neutral-relaxing conditions differ in individuals with addictions to cocaine or alcohol from those without these addictions. Our findings indicate that subjects with cocaine or alcohol dependence show relatively greater activations within limbic regions and diminished activation within prefrontal cortex as compared to control comparison subjects. The extent to which similar patterns extend or do not to tobacco smokers or obese people has important clinical implications. That is, the identification of common and unique neural substrates to tobacco smoking and obesity has important implications not only for how we conceptualize the disorders, but also for the development of improved prevention and treatment strategies for these conditions that currently impact millions of people in the United States. The examination of the influence of self-control and related constructs in relation to the fMRI measures in the tobacco smoking and obese groups should provide additional information with relevance to the development of targeted prevention and treatment strategies.